Nuclear factor kappa-light-chain-enhancer of activated B cells signaling components (NF-κB signaling)

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling components comprise a family of inducible transcription factors and their regulatory proteins that serve as master regulators of the immune response, inflammation, and cell survival. The core of the pathway includes the NF-κB protein family (RelA/p65, RelB, c-Rel, p50, and p52), which exist as dimers sequestered in the cytoplasm by inhibitory IκB proteins. Activation is typically triggered by the IκB kinase (IKK) complex, which phosphorylates IκB in response to stimuli like cytokines (e.g., TNF-α, IL-1) or pathogens, leading to IκB degradation and the subsequent nuclear translocation of NF-κB to initiate gene transcription. Dysregulation of this pathway is central to the pathogenesis of chronic inflammatory diseases, autoimmune disorders, and various cancers, where constitutive NF-κB activity promotes tumor growth, angiogenesis, and resistance to chemotherapy. Consequently, the pathway is a major therapeutic target, with drugs such as proteasome inhibitors (e.g., bortezomib) and IKK inhibitors designed to suppress its activity. However, the essential role of NF-κB in maintaining normal immunity and cellular homeostasis presents significant challenges, as systemic inhibition can lead to severe immunosuppression and other adverse effects.

Other names

NF-kappaB pathwayNF-κB/Rel signalingIκB kinase/NF-κB signalingNuclear factor-kappa B signaling cascade

Inhibition of IκB kinase (IKK) activity, inhibition of the 26S proteasome to prevent IκB degradation, blockade of NF-κB nuclear translocation, and interference with NF-κB DNA binding.